BAP1-related tumor predisposition syndrome

Summary

BAP1-related tumor predisposition syndrome (MONDO:0013692) is a cancer caused by BAP1 (GenCC Definitive), with 6 cohort genes (2 CIViC-evidence somatic drivers; 2,594 ClinVar predisposition records) and 3 clinical trials. The dominant Reactome pathway is DNA Double-Strand Break Repair (3 cohort genes).

At a glance

• Classification: Cancer
• Prevalence: Unknown (Worldwide)
• Causal gene: BAP1 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 2,594
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	BAP1-related tumor predisposition syndrome
Mondo ID	MONDO:0013692
OMIM	614327
Orphanet	289539
NCIT	C172639
SNOMED CT	765057007
UMLS	C3280492
MedGen	482122
GARD	0013219
Is cancer (heuristic)	yes

Also known as: BAP1 tumor predisposition syndrome · BAP1 tumour predisposition syndrome · BAP1-related tumor predisposition syndrome · TPDS · tumor predisposition syndrome · tumor susceptibility linked to germline BAP1 mutations · tumour predisposition syndrome · tumour susceptibility linked to germline BAP1 mutations

Data availability: 2,594 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › BAP1-related tumor predisposition syndrome

Related subtypes (116): mosaic variegated aneuploidy syndrome, tuberous sclerosis, hereditary breast ovarian cancer syndrome, hereditary multiple osteochondromas, nevoid basal cell carcinoma syndrome, leukemia, chronic lymphocytic, susceptibility to, 2, blue rubber bleb nevus, cherubism, Beckwith-Wiedemann syndrome, multiple self-healing squamous epithelioma, erythroleukemia, familial, susceptibility to, goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, hyperparathyroidism 2 with jaw tumors, Kaposi sarcoma, susceptibility to, hereditary leiomyomatosis and renal cell cancer, susceptibility to uveal melanoma, melanoma and neural system tumor syndrome, nasopharyngeal carcinoma, susceptibility to, 2, WAGR syndrome, neuroblastoma, susceptibility to, 1, Rothmund-Thomson syndrome, mismatch repair cancer syndrome 1, Wiskott-Aldrich syndrome, N syndrome, hereditary thrombocytopenia and hematologic cancer predisposition syndrome, prostate cancer/brain cancer susceptibility, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, ovarian cancer, susceptibility to, 1, colorectal cancer, susceptibility to, 1, lung cancer susceptibility 1, leukemia, chronic lymphocytic, susceptibility to, 1, Kostmann syndrome, colorectal cancer, susceptibility to, 2, colorectal cancer, susceptibility to, 3, colorectal cancer, susceptibility to, 5, colorectal cancer, susceptibility to, 6, colorectal cancer, susceptibility to, 7, leukemia, chronic lymphocytic, susceptibility to, 3, leukemia, chronic lymphocytic, susceptibility to, 4, leukemia, chronic lymphocytic, susceptibility to, 5, lung cancer susceptibility 3, colorectal cancer, susceptibility to, 8, colorectal cancer, susceptibility to, 9, colorectal cancer, susceptibility to, 10, colorectal cancer, susceptibility to, 11, lung cancer susceptibility 4, neuroblastoma, susceptibility to, 3, neuroblastoma, susceptibility to, 4, neuroblastoma, susceptibility to, 5, neuroblastoma, susceptibility to, 6, leukemia, acute lymphocytic, susceptibility to, 1, leukemia, acute lymphocytic, susceptibility to, 2, lung cancer susceptibility 5, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, basal cell carcinoma, susceptibility to, 7, colorectal cancer, susceptibility to, 12, leukemia, acute lymphoblastic, susceptibility to, 3, cholangiocarcinoma, susceptibility to, progeroid features-hepatocellular carcinoma predisposition syndrome, neuroblastoma, susceptibility to, 7, DDX41-related hematologic malignancy predisposition syndrome, nasopharyngeal carcinoma, susceptibility to, 3, familial isolated hyperparathyroidism, intestinal polyposis syndrome, dyskeratosis congenita, familial rhabdoid tumor, multiple endocrine neoplasia, hereditary pheochromocytoma-paraganglioma, PTEN hamartoma tumor syndrome, familial multiple fibrofolliculoma, hereditary retinoblastoma, familial atypical multiple mole melanoma syndrome, hereditary nonpolyposis colon cancer, Li-Fraumeni syndrome, Cobb syndrome, neurofibromatosis, susceptibility to familial cutaneous melanoma, pancreatic cancer, susceptibility to, 5, leukemia, acute myeloid, susceptibility to, diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, glioma susceptibility, hemangioma, capillary infantile, susceptibility to, CDH1-related diffuse gastric and lobular breast cancer syndrome, NTHL1-deficiency tumor predisposition syndrome, SAMD9-related spectrum and myeloid neoplasm risk, neuroblastoma, susceptibility to, 2, BARD1-related cancer predisposition, BRCA1-related cancer predisposition, BRCA2-related cancer predisposition, ATM-related cancer predisposition, CHEK2-related cancer predisposition, PALB2-related cancer predisposition, RAD51C-related cancer predisposition, RAD51D-related cancer predisposition, Li-fraumeni-like syndrome, breast cancer, familial, susceptibility to, 1, breast cancer, familial, susceptibility to, 2, breast cancer, familial, susceptibility to, 3, colorectal cancer, susceptibility to, 4, colorectal cancer, susceptibility to, on chromosome 15, ovarian cancer, familial, susceptibility to, 1, ovarian cancer, familial, susceptibility to, 2, ovarian cancer, familial, susceptibility to, 3, inherited hematologic cancer-predisposing syndrome, mosaic neurofibromatosis/schwannomatosis, tumor predisposition syndrome 2, prostate cancer, hereditary, X-linked 3, follicular lymphoma, susceptibility to, GPR161-related medulloblastoma predisposition, SAMD9L-related spectrum and myeloid neoplasm risk, HAVCR2-related cancer predisposition, EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

222 uncertain significance, 175 likely benign, 69 conflicting classifications of pathogenicity, 67 benign/likely benign, 48 pathogenic, 11 likely pathogenic, 6 pathogenic/likely pathogenic, 1 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012196	NM_004656.4(BAP1):c.67+2T>C	BAP1	Pathogenic	criteria provided, single submitter
1068233	NM_004656.4(BAP1):c.1730-2A>G	BAP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069122	NM_004656.4(BAP1):c.593dup (p.Asp199fs)	BAP1	Pathogenic	criteria provided, single submitter
1070605	NM_004656.4(BAP1):c.1883C>A (p.Ser628Ter)	BAP1	Pathogenic	criteria provided, single submitter
1070749	NM_004656.4(BAP1):c.799_800del (p.Gln267fs)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070831	NM_004656.4(BAP1):c.1470_1471insA (p.Glu491fs)	BAP1	Pathogenic	criteria provided, single submitter
1071620	NM_004656.4(BAP1):c.2017G>T (p.Glu673Ter)	BAP1	Pathogenic	criteria provided, single submitter
1071927	NM_004656.4(BAP1):c.669C>A (p.Tyr223Ter)	BAP1	Pathogenic	criteria provided, single submitter
1072297	NM_004656.4(BAP1):c.436dup (p.Arg146fs)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1073043	NM_004656.4(BAP1):c.944dup (p.Ala316fs)	BAP1	Pathogenic	criteria provided, single submitter
1073050	NM_004656.4(BAP1):c.203del (p.Asp68fs)	BAP1	Pathogenic	criteria provided, single submitter
1073322	NM_004656.4(BAP1):c.581-2A>G	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1073405	NM_004656.4(BAP1):c.132T>G (p.Tyr44Ter)	BAP1	Pathogenic	criteria provided, single submitter
1073757	NM_004656.4(BAP1):c.830_831del (p.Gln277fs)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1073906	NM_004656.4(BAP1):c.721dup (p.Tyr241fs)	BAP1	Pathogenic	criteria provided, single submitter
1074027	NM_004656.4(BAP1):c.122+1G>T	BAP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074041	NM_004656.4(BAP1):c.555del (p.Gly185_Leu186insTer)	BAP1	Pathogenic	criteria provided, single submitter
1075173	NM_004656.4(BAP1):c.102_109del (p.Asp34fs)	BAP1	Pathogenic	criteria provided, single submitter
1075700	NM_004656.4(BAP1):c.1766_1770del (p.Ile589fs)	BAP1	Pathogenic	criteria provided, single submitter
1076668	NM_004656.4(BAP1):c.1383dup (p.Pro462fs)	BAP1	Pathogenic	criteria provided, single submitter
1338674	NM_004656.4(BAP1):c.1588del (p.Val530fs)	BAP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1362781	NM_004656.4(BAP1):c.1778del (p.Gln593fs)	BAP1	Pathogenic	criteria provided, single submitter
1365414	NM_004656.4(BAP1):c.1139_1151del (p.Gly380fs)	BAP1	Pathogenic	criteria provided, single submitter
1386236	NM_004656.4(BAP1):c.606_607delinsTT (p.Trp202_Thr203delinsCysSer)	BAP1	Pathogenic	criteria provided, single submitter
1396376	NM_004656.4(BAP1):c.1786del (p.Ser596fs)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1399300	NM_004656.4(BAP1):c.604T>C (p.Trp202Arg)	BAP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1417901	NM_004656.4(BAP1):c.49dup (p.Leu17fs)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1421770	NM_004656.4(BAP1):c.119_120del (p.Gln40fs)	BAP1	Pathogenic	criteria provided, single submitter
1422258	NM_004656.4(BAP1):c.1661del (p.Gly554fs)	BAP1	Pathogenic	criteria provided, single submitter
1425452	NM_004656.4(BAP1):c.1793del (p.Pro598fs)	BAP1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 28 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BAP1	Definitive	Autosomal dominant	BAP1-related tumor predisposition syndrome	9
MAGI1	Definitive	Autosomal dominant	BAP1-related tumor predisposition syndrome	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BAP1	Orphanet:2495	Meningioma
BAP1	Orphanet:289539	BAP1-related tumor predisposition syndrome
BAP1	Orphanet:39044	Uveal melanoma
BAP1	Orphanet:50251	Pleural mesothelioma
BAP1	Orphanet:528084	Non-specific syndromic intellectual disability
BAP1	Orphanet:618	Familial melanoma
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
DNAH1	Orphanet:244	Primary ciliary dyskinesia
DNAH1	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MAGI1	HGNC:946	ENSG00000151276	Q96QZ7	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1	gencc,clinvar
BAP1	HGNC:950	ENSG00000163930	Q92560	Ubiquitin carboxyl-terminal hydrolase BAP1	gencc,clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
PHF7	HGNC:18458	ENSG00000010318	Q9BWX1	E3 ubiquitin-protein ligase PHF7	clinvar
DNAH1	HGNC:2940	ENSG00000114841	Q9P2D7	Dynein axonemal heavy chain 1	clinvar
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAGI1	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1	Plays a role in coupling actin fibers to cell junctions in endothelial cells, via its interaction with AMOTL2 and CDH5.
BAP1	Ubiquitin carboxyl-terminal hydrolase BAP1	Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
PHF7	E3 ubiquitin-protein ligase PHF7	E3 ubiquitin-protein ligase which ubiquitinates histone H3 at ‘Lys-14’.
DNAH1	Dynein axonemal heavy chain 1	Force generating protein of cilia required for sperm flagellum motility.
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	2	9.2×	0.071
Protease	1	6.1×	0.306
Transcription factor	1	1.4×	0.719
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAGI1	Kinase	yes		WW_dom, PDZ, Guanylate_kin-like_dom
BAP1	Protease	yes	3.4.19.12	Peptidase_C12_UCH, Peptidase_C12_UCH_sf, Papain-like_cys_pep_sf
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
PHF7	Transcription factor	no		Znf_RING, Znf_PHD, Znf_FYVE_PHD
DNAH1	Other/Unknown	no		Dhc_D6_P-loop, Dhc_linker, Dhc_D4
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom

Expression context

Cohort genes with no expression data: 0.

6 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	2
ventricular zone	2
left testis	2
right testis	2
sural nerve	1
right frontal lobe	1
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1
adult organism	1
bronchial epithelial cell	1
bronchus	1
right uterine tube	1
calcaneal tendon	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAGI1	133	ubiquitous	marker	ventricular zone, sural nerve, corpus callosum
BAP1	253	ubiquitous	marker	left testis, right testis, right frontal lobe
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
PHF7	215	ubiquitous	marker	right testis, left testis, adult organism
DNAH1	183	tissue_specific	marker	right uterine tube, bronchial epithelial cell, bronchus
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATM	7,383
BRCA2	4,839
BAP1	3,373
MAGI1	2,043
DNAH1	1,699
PHF7	1,626

Intra-cohort edges

A	B	Sources
ATM	BRCA2	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAGI1	Q96QZ7	16
BRCA2	P51587	14
ATM	Q13315	14
BAP1	Q92560	4
DNAH1	Q9P2D7	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PHF7	Q9BWX1	76.11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 68. Enrichment computed across 6 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
DNA Double-Strand Break Repair	3	248.3×	4e-06	BAP1, BRCA2, ATM
DNA Repair	3	98.5×	3e-05	BAP1, BRCA2, ATM
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2	634.4×	6e-05	BRCA2, ATM
Diseases of DNA Double-Strand Break Repair	2	543.8×	6e-05	BRCA2, ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2	543.8×	6e-05	BRCA2, ATM
Resolution of D-Loop Structures	2	423.0×	8e-05	BRCA2, ATM
Diseases of DNA repair	2	380.7×	8e-05	BRCA2, ATM
DNA Double Strand Break Response	2	317.2×	9e-05	BAP1, ATM
Impaired BRCA2 binding to PALB2	2	304.5×	9e-05	BRCA2, ATM
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	282.0×	9e-05	BRCA2, ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	282.0×	9e-05	BRCA2, ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	282.0×	9e-05	BRCA2, ATM
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	262.5×	1e-04	BRCA2, ATM
Homologous DNA Pairing and Strand Exchange	2	253.8×	1e-04	BRCA2, ATM
Homology Directed Repair	2	205.8×	1e-04	BRCA2, ATM
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2	205.8×	1e-04	BRCA2, ATM
Impaired BRCA2 binding to RAD51	2	205.8×	1e-04	BRCA2, ATM
Resolution of D-loop Structures through Holliday Junction Intermediates	2	200.3×	1e-04	BRCA2, ATM
Meiosis	2	190.3×	1e-04	BRCA2, ATM
Presynaptic phase of homologous DNA pairing and strand exchange	2	181.3×	1e-04	BRCA2, ATM
Reproduction	2	126.9×	3e-04	BRCA2, ATM
HDR through Homologous Recombination (HRR)	2	126.9×	3e-04	BRCA2, ATM
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	2	97.6×	4e-04	BAP1, ATM
Meiotic recombination	2	86.5×	5e-04	BRCA2, ATM
Impaired BRCA2 translocation to the nucleus	1	1268.9×	0.002	BRCA2
Impaired BRCA2 binding to SEM1 (DSS1)	1	1268.9×	0.002	BRCA2
Sensing of DNA Double Strand Breaks	1	634.4×	0.004	ATM
Cell Cycle	2	24.0×	0.005	BRCA2, ATM
TP53 Regulates Transcription of Caspase Activators and Caspases	1	317.2×	0.007	ATM
Pexophagy	1	317.2×	0.007	ATM

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
thrombocyte differentiation	1	2808.7×	0.008	BAP1
nucleate erythrocyte differentiation	1	2808.7×	0.008	BAP1
leukocyte proliferation	1	1404.3×	0.008	BAP1
establishment of RNA localization to telomere	1	1404.3×	0.008	ATM
establishment of protein-containing complex localization to telomere	1	1404.3×	0.008	ATM
positive regulation of telomerase catalytic core complex assembly	1	1404.3×	0.008	ATM
mitotic recombination-dependent replication fork processing	1	1404.3×	0.008	BRCA2
DNA damage response, signal transduction by p53 class mediator	2	119.5×	0.008	BRCA2, ATM
cellular senescence	2	98.5×	0.008	BRCA2, ATM
double-strand break repair	2	67.7×	0.008	BRCA2, ATM
double-strand break repair via homologous recombination	2	52.0×	0.008	BRCA2, ATM
pre-B cell allelic exclusion	1	936.2×	0.009	ATM
platelet morphogenesis	1	936.2×	0.009	BAP1
macrophage homeostasis	1	936.2×	0.009	BAP1
cellular response to nitrosative stress	1	936.2×	0.009	ATM
negative regulation of osteoclast proliferation	1	936.2×	0.009	PHF7
negative regulation of mammary gland epithelial cell proliferation	1	561.7×	0.012	BRCA2
peptidyl-serine autophosphorylation	1	561.7×	0.012	ATM
negative regulation of telomere capping	1	561.7×	0.012	ATM
regulation of telomere maintenance via telomerase	1	468.1×	0.013	ATM
positive regulation of telomere maintenance via telomere lengthening	1	468.1×	0.013	ATM
lipoprotein catabolic process	1	401.2×	0.013	ATM
myeloid cell apoptotic process	1	351.1×	0.013	BAP1
V(D)J recombination	1	351.1×	0.013	ATM
establishment of protein localization to telomere	1	351.1×	0.013	BRCA2
neutrophil differentiation	1	312.1×	0.013	BAP1
monoubiquitinated protein deubiquitination	1	312.1×	0.013	BAP1
common myeloid progenitor cell proliferation	1	312.1×	0.013	BAP1
meiotic telomere clustering	1	312.1×	0.013	ATM
regulation of cytokine production involved in inflammatory response	1	312.1×	0.013	BAP1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 3 of 6 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ATM	AMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATM	35	4
MAGI1	0	0
BAP1	0	0
BRCA2	0	0
PHF7	0	0
DNAH1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
DACTOLISIB	3	ATM
STREPTONIGRIN	2	ATM
CALCIMYCIN	2	ATM
ENPIROLINE	2	ATM
OXACEPROL	2	ATM
TOLONIUM CHLORIDE	2	ATM
ESTRADIOL BENZOATE	2	ATM
BERZOSERTIB	2	ATM
LARTESERTIB	2	ATM
ALTHIAZIDE	2	ATM

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ATM	240	Binding:233, Functional:5, ADMET:2
BAP1	5	Binding:4, Functional:1
MAGI1	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BAP1	3.4.19.12	ubiquitinyl hydrolase 1
ATM	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ATM	240

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
DACTOLISIB	3	ATM
STREPTONIGRIN	2	ATM
CALCIMYCIN	2	ATM
ENPIROLINE	2	ATM
OXACEPROL	2	ATM
TOLONIUM CHLORIDE	2	ATM
ESTRADIOL BENZOATE	2	ATM
BERZOSERTIB	2	ATM
LARTESERTIB	2	ATM
ALTHIAZIDE	2	ATM

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATM
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	MAGI1, BAP1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	BRCA2, PHF7, DNAH1

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MAGI1	4	—
BAP1	5	—
BRCA2	0	—
PHF7	0	—
DNAH1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT04431024	Not specified	RECRUITING	Prospective Evaluation of High Resolution Dual Energy Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients With BAP1 Tumor Predisposition Syndrome
NCT05534854	Not specified	UNKNOWN	Frequency, Clinical Phenotype and Genetic Analysis of Heritable Kidney Cancer Syndromes